AIMS: The goal of this application is to apply for Research Career Scientist (RCS) Award and to support Dr. Huiping Zhou?s VA research program. NOMINEE: Dr. Zhou has held a VA Research Chemist position since 2008, and she also holds the title of Tenured Professor in the Department of Microbiology and Immunology at Virginia Commonwealth University School of Medicine in Richmond, Virginia. Dr. Zhou?s research program has been continuously funded by VA MERIT Review Awards, NIH R01 grants, several local foundations and pharmaceutical companies since she established her independent research program in 2004. Dr. Zhou has made significant contributions to scientific research fields related to liver injury and metabolic diseases throughout her career, and published more than 100 peer- reviewed original research articles that have created more than 6000 citations. In addition, Dr. Zhou acts as a co-investigator in several VA-sponsored research projects. Research: Studies in Dr. Zhou?s laboratory are to investigate the mechanisms underlying drug- induced liver injury and the role of bile acid-mediated signaling pathways in hepatic lipid metabolism under physiological and pathological conditions, and to further search for new and more effective therapies to prevent and treat metabolic diseases. Disruption of hepatic bile acid homeostasis occur commonly in various pathological states such as non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (ALD), cholestatic liver diseases as well as drug- induced liver injury. Since the exact mechanisms underlying bile acid-mediated liver injury and metabolic diseases are still obscure, effective therapeutics are limited. Dr. Zhou?s research is highly focused on identification of novel cellular/molecular mechanisms involved in disease progression of NAFLD, ALD and cholestatic liver diseases. Dr. Zhou?s research employs the stat- of-the-art techniques, including isolation and culture of various hepatic cells, examine specific messenger RNA (mRNA), non-coding RNA (ncRNA), mRNA/ncRNA/RNA ?binding proteins (RBP) interactions and extracellular vehicles-mediated communications. Dr. Zhou?s group has established animal models for NAFLD/NASH, ALD, and cholestasis. Her group has also extensively used genetic modified animals including tissue-specific knockout mice. The overreaching goal of Dr. Zhou?s research program is to elucidate the cellular/molecular mechanisms that govern hepatic lipid homeostasis and to create a fundamental base for development of new therapeutics for various liver diseases. IMPACT: Dr. Zhou?s research program directly addresses an important health issue relevant to the VA mission, since NAFLD/NASH, ALD and cholestatic liver diseases occur commonly in our VA patient population. Dr. Zhou is also actively collaborates a number of investigators in the Research service of the McGuire VA Medical Center. Her expertise and academic activity help promoting VAMHCS research.